Objective: Analysis of functionally defined T-cell differentiation in HIV-infected patients with low CD4 on virologically suppressive HAART is crucial to design clinically efficacious treatments. Methods: We cross-sectionally investigated the maturation (CD45RA/CCR7, CD7) and function [antigen-specific enzyme-linked immunosorbent spot assay (ELISPOT), interleukin-2 (IL-2)/interferon-γ-producing cells] of CD4 and CD8+ T cells in 34 HIV-infected immunological nonresponders (INRs): CD4 cell count less than or equal to 200 cells/μl, HIV-RNA 50 copies/ml or less, as compared to 20 full responders (CD4 > 500 cells/μl, HIV-RNA < 50 copies/ml). Results: We describe skewed T-cell maturation in INRs with outgrowth of effector memory CD45RACCR7 CD4/CD8+ and Th2-committed CD7CD4, and reduced unprimed-naive T cells (P = 0.001). Functionally, INRs display reduced Gag-specific ELISPOT (P = 0.04) and IL-2-secreting CD8+ (P = 0.08) while showing CMV-specific responses comparable to full responders. Conclusion: CD4 lymphopenia on HAART results in skewed, senescent T-cell maturation profile, inefficient T-helper function and poor HIV-specific CD8+ response. This delineates a functional/phenotypic T-cell pattern that correlates to unfavourable clinical outcome.
Skewed T-cell maturation and function in HIV-infected patients failing CD4+ recovery upon long-term virologically suppressive HAART / G.C. Marchetti, L. Gazzola, D.L. Trabattoni, F. Bai, G. Ancona, L. Ferraris, L. Meroni, M. Galli, M.S. Clerici, A. Gori, A. d'Arminio Monforte. - In: AIDS. - ISSN 0269-9370. - 24:10(2010), pp. 1455-1460. [10.1097/QAD.0b013e328339cf40]
Skewed T-cell maturation and function in HIV-infected patients failing CD4+ recovery upon long-term virologically suppressive HAART
G.C. Marchetti
;L. GazzolaSecondo
;D.L. Trabattoni;F. Bai;G. Ancona;L. Ferraris;M. Galli;M.S. Clerici;A. Gori;A. d'Arminio MonforteUltimo
2010
Abstract
Objective: Analysis of functionally defined T-cell differentiation in HIV-infected patients with low CD4 on virologically suppressive HAART is crucial to design clinically efficacious treatments. Methods: We cross-sectionally investigated the maturation (CD45RA/CCR7, CD7) and function [antigen-specific enzyme-linked immunosorbent spot assay (ELISPOT), interleukin-2 (IL-2)/interferon-γ-producing cells] of CD4 and CD8+ T cells in 34 HIV-infected immunological nonresponders (INRs): CD4 cell count less than or equal to 200 cells/μl, HIV-RNA 50 copies/ml or less, as compared to 20 full responders (CD4 > 500 cells/μl, HIV-RNA < 50 copies/ml). Results: We describe skewed T-cell maturation in INRs with outgrowth of effector memory CD45RACCR7 CD4/CD8+ and Th2-committed CD7CD4, and reduced unprimed-naive T cells (P = 0.001). Functionally, INRs display reduced Gag-specific ELISPOT (P = 0.04) and IL-2-secreting CD8+ (P = 0.08) while showing CMV-specific responses comparable to full responders. Conclusion: CD4 lymphopenia on HAART results in skewed, senescent T-cell maturation profile, inefficient T-helper function and poor HIV-specific CD8+ response. This delineates a functional/phenotypic T-cell pattern that correlates to unfavourable clinical outcome.File | Dimensione | Formato | |
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